The number of patients with a renal disease such as patients with renal failure, particularly the number of patients undergoing renal dialysis is constantly on the rise every year. At present, two hundred thousand patients receive maintenance dialysis therapy, and an additional thirty thousand or more people start dialysis every year. The annual cost of dialysis therapy is approximately five million yen per individual, meaning that medical care cost of approximately a trillion yen is constantly required for two hundred thousand people. Also, recently, a disease concept of Chronic Kidney Disease (CKD) has been proposed, raising awareness of the importance of prevention and treatment of CKD. In light of the fact that CKD is a common disease with the population of people having a glomerular filtration rate (GFR) of less than 60 reaching as high as 19.26 million, countermeasures against CKD are urgently needed. Under the foregoing circumstances, if a preventive method for symptoms of a renal disease such as renal failure and CKD and a therapeutic method capable of alleviating such symptoms and delaying introduction of dialysis can be developed, then not only a contribution is made to Quality Of Life (QOL) of the patients but also medical care cost can be reduced considerably, making a great contribution to the society.
When an individual suffers from renal failure, various substances that would be excreted from the kidney in a healthy state accumulate in the body. These substances are occasionally utilized as marker substances in the diagnosis of renal failure. For example, a method of detecting/diagnosing a renal disease by using an increase in a marker protein for a renal disease such as albumin excreted in urine as an index is commonly employed. As other methods, for example, a method for detecting a renal disease utilizing an elevated blood concentration of human lipocalin-type prostaglandin D synthase in patients with a renal disease (see patent document 1) and a method for diagnosing nephropathy utilizing elevated blood and urinary concentrations of ENDO180 receptor polypeptide in patients with renal failure and the like (see patent document 2) are known.
Also, among the aforementioned substances that accumulate in the body of an individual suffering from renal failure, a substance that is toxic to the living body is referred to as a so-called renal failure substance, which has been reported as a substance that aggravates the pathological condition of renal failure per se. However, most of the presently used renal failure marker substances such as creatinine reflect glomerular filtration rate (GFR), where glomerular filtration is a part of renal function, and few of them reflect other renal functions such as tubular function. Also, because creatinine has a creatinine blind GFR area, which does not reflect renal function (i.e., a period in which an increase in creatinine remains unrecognizable despite aggravation of renal function), it has been unsatisfactory as a renal failure marker substance. Further, it is difficult to evaluate various symptoms of renal failure in an integrated fashion with the existing marker substances. Also, substances involved in aggravation of renal failure and the mechanism of aggravation of renal failure have remained largely unknown.
Meanwhile, capillary electrophoresis mass spectrometry (CE-MS) is a recently developed new system, which enables simultaneous measurement of 500 or more kinds of substances from a small amount of sample.